The PONTI study: inositol and prevention of NTDs

Some cases of NTD can be prevented by supplementation with folic acid before and during early pregnancy, but it is increasingly apparent that a significant proportion of NTDs fail to respond to FA. Most programmes of voluntary supplementation and folic acid food-fortification have observed a reduction in NTD prevalence of less than 50%.

As a result, NTDs continue to occur at an average frequency of 0.5-1.0 per 1000 established pregnancies, worldwide. We have explored the possibility that inositol, a vitamin-like molecule with a key role in cellular metabolism, has a NTD-preventive action that is independent of folic acid. If confirmed, this could lead to a combined approach to primary prevention of NTDs, involving both folic acid and inositol supplements.

IN PREVIOUS WORK, THE NEURAL TUBE GROUP HAS:

Established that both myo- and D-chiro-inositol can significantly reduce the frequency of spinal NTDs in curly tail (Grhl3 gene) mice, both by dosing the pregnant female, and by direct treatment of embryos in culture (Greene & Copp, 1997; Cogram et al, 2002).

Shown inositol therapy to be safe in mouse pregnancy, with no adverse effects noted in either mothers or fetuses (Cogram et al, 2002).

Developed a mass-spectrometry-based assay for inositol in biological samples (Leung et al, 2011).

The PONTI pilot study

PONTI: Prevention ofNeural Tube Defects by Inositol

UK women with a history of NTD pregnancy were recruited into a double-blind, randomised controlled trial of myo-inositol supplementation before and during early pregnancy. The pilot study was designed to provide information on the following primary outcomes:

to determine the feasibility of recruiting,
randomising and following-up women with a history of NTD pregnancy, who
are embarking upon a further pregnancy

to gather preliminary data on NTD recurrence frequency in the UK trial setting

to determine the safety of inositol administration during the peri-conceptional period and first trimester of pregnancy

to assess compliance with supplementation using the mass spectrometry-based assay for inositol